106294-20-6Relevant articles and documents
Synthesis and biological evaluation of 3-tetrazolo steroidal analogs: Novel class of 5α-reductase inhibitors
Aggarwal, Saurabh,Mahapatra, Manoj Kumar,Kumar, Rajnish,Bhardwaj, Tilak R.,Hartmann, Rolf W.,Haupenthal, J?rg,Kumar, Manoj
, p. 779 - 788 (2016)
In the present study, a series of steroidal tetrazole derivatives of androstane and pregnane have been prepared in which the tetrazole moiety was appended at C-3 and 17a-aza locations. 3-Tetrazolo-3,5-androstadien-17-one (6), 3-tetrazolo-19-nor-3,5-androstadien-17-one (10), 3-tetrazolo-3,5-pregnadien-20-one (14), 17a-substituted 3-tetrazolo-17a-aza-d-homo-3,5-androstadien-17-one (26-31) and 3-(2-acetyltetrazolo)-17a-aza-d-homo-3,5-androstadien-17-one (32) were synthesized from dehydroepiandrosterone acetate (1) through multiple synthetic steps. Some of the synthesized compounds were evaluated for their in vitro 5α-reductase (5AR) inhibitory activity by measuring the conversion of [3H] androstenedione in human embryonic kidney (HEK) cells. In vivo 5α-reductase inhibitory activity also showed a significant reduction (p 50 being 15.6 nM as compared to clinically used drug finasteride (40 nM). There was also a significant inhibition of 5AR-1 with IC50 547 nM compared to finasteride (453 nM).
Synthesis and cytotoxicity of 17a-aza-d-homo-androster-17-one derivatives
Huang, Yanmin,Cui, Jianguo,Zhong, Zhengguo,Gan, Chunfang,Zhang, Wenyan,Song, Huacan
, p. 3641 - 3643 (2011)
A series of 17a-aza-D-homo-andrester-17-one derivatives, bearing hydroxyl, hydroximino, carbonyl and thiosemicarbazido groups at the position-3 or position-6 of steroidal nucleus, were prepared and evaluated in vitro against two human cell lines (Hela (human cervical carcinoma) and SMMC 7404 (human liver carcinoma)). The results showed that these compounds could exhibit a high cytotoxicity to Hela tumor cell line, especially for compounds 8 and 12, the IC50 values are 15.1 and 14.0 nmol/mL, respectively. Our findings could provide new evidence showing the relationship between the chemical structure and biological activity and may be useful for the discovery of new anti-cancer drugs.
Protein-binding properties of a designed steroidal lactam compound
Zhang, Hua-Xin,Liu
, p. 30 - 36 (2014)
Introducing amide bonds into a steroid nucleus or its side chain may reduce the acute toxicity and enhance the pharmaceutical activity. In this work, a designed steroidal amide compound, named 3β-hydroxy-17-aza-d-homo-5- androsten-17-one (HAAO), was synthesized and identified. The interactions between HAAO and human serum albumin (HSA) were studied by multiple spectroscopic methods and molecular modeling procedures. It was found that HAAO locates in Sudlow's site I in subdomain IIA of HSA molecules, relying on hydrogen bonds and van der Waals power to form HAAO-HSA complexes at ground state. The number of binding sites, binding constants, enthalpy change (ΔHθ), Gibbs free energy change (ΔG θ) and entropy change (ΔSθ) were calculated at different temperatures based on fluorescence quenching theory and classical thermodynamic equation. The percentages content of the HSA's secondary structures in presence of HAAO were detected by circular dichroism (CD) spectra and compared with those in no presence of HAAO. In addition, the experimental results of both binding site and conformational change were further confirmed by molecular modeling investigation, in which more details of the binding were visually unfolded. The information provided by the study may be useful for designing novel chemotherapeutic drugs and be helpful both in the early stages of drug discovery and in clinical practice.
Copper-Catalyzed Aza-Sonogashira Cross-Coupling To Form Ynimines: Development and Application to the Synthesis of Heterocycles
Lavernhe, Rémi,Torres-Ochoa, Rubén O.,Wang, Qian,Zhu, Jieping
supporting information, p. 24028 - 24033 (2021/10/07)
Nitrogen-substituted alkynes, such as ynamines and ynamides, are versatile synthetic building blocks. Ynimines bearing additional nucleophilic and electrophilic centers relative to ynamines and ynamides are expected to have high synthetic potential. However, their chemical reactivity remains unexplored owing mainly to the lack of synthetic accessibility. We report herein a versatile copper-catalyzed synthesis of ynimines from readily available O-acetyl ketoximes and terminal alkynes. A wide range of O-acetyl ketoximes derived from diaryl ketones, aryl alkyl ketones and dialkyl ketones underwent cross-coupling with a diverse set of terminal alkynes to afford the ynimines in good to excellent yields. An unprecedented [5+1] heteroannulation reaction exploiting the reactivity of the ynimine generated in situ was subsequently developed for the synthesis of medicinally important heterocycles, including isoquinolines, azaindoles, azabenzofurans, azabenzothiophenes and carbolines.
Mild, calcium catalysed Beckmann rearrangements
Kiely-Collins,Sechi,Brennan,McLaughlin
supporting information, p. 654 - 657 (2018/02/06)
A mild calcium catalysed Beckmann rearrangement has been realised, which forgoes the more traditional harsh reactions conditions associated with the transformation. The catalyst system is shown to be tolerant towards a wide variety of functional groups relevant to natural product synthesis and medicinal chemistry and the synthetic utility of the reaction has also been investigated. A preliminary mechanistic investigation was performed to understand the nature of the incoming nucleophile and a possible reaction pathway is described.
